This first grant application by this investigator will examine the relationship between chronic distress and natural killer (NK) cell function across the menstrual cycle in women with and without a symptomatic chronic health disturbance (irritable bowel syndrome, IBS). NK cells are part of the innate immune system and are involved in the early recognition of foreign antigens and the destruction of foreign antigen-bearing cells. IBS is a heterogeneous, chronic, non-inflammatory condition. Ongoing physical and psychological distress, coupled with recent evidence of enhanced physiological arousal, characterize this chronic health disturbance. Prior research by others has documented elevated stress hormone levels in women with IBS. Preliminary data suggest innate immune function differs in women with and without symptomatic IBS. Because IBS is not an inflammatory disease process, women with IBS are ideal subjects to utilize when examining the relationships among distress, ovarian hormone levels, physiological arousal indicators, and NK cell activity and numbers. The purpose of this study is to compare innate immune function across the menstrual cycle in normally menstruating women with and without IBS. The specific aims of this study are to: 1) describe the levels of specific immune function markers across 3 menstrual cycle phases, and test for cycle phase and group differences in normally menstruating women with and without IBS; 2) extend and affirm the work of others by describing levels of stress hormones, physical distress, psychological distress, and ovarian hormone levels across 3 menstrual cycle phases, and by testing for cycle phase and group differences in these variables; and 3) examine the relationship of immune function to measures of physiological arousal, physical and psychological distress, and ovarian hormones during each menstrual cycle phase. Descriptive and correlational statistics and repeated measures ANOVA will be used in data analysis. If a relationship does exist between chronic distress and NK cell function, there would be important clinical implications for identifying women at risk for experiencing chronic distress and depressed innate immunity, and for developing and testing interventions targeting distress reduction in vulnerable populations. Additionally, this study is a first step to understanding the potential influence of the menstrual cycle in innate immune function in women with inflammatory conditions.